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Faculty Detail     Name BORIS C PASCHE   Campus Address NP 2566 Zip 3300 Phone 205-934-9591 E-mail uifcftu@uab.edu Other websites

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Medicine  Med - Hematology & Oncology Professor Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor Center  General Clinical Research Center  Minority Health & Research Center Professor

Graduate Biomedical Sciences Affiliations Cancer Biology  Cell, Molecular, & Developmental Biology  Genetics and Genomic Sciences  Medical Scientist Training Program  Pathobiology and Molecular Medicine

Biographical Sketch  Education and degrees 1980-1983 University of Lausanne, Lausanne, Switzerland 1983-1989 Karolinska Institute, Stockholm, Sweden 1986 M.D. degree, Karolinska Institute 1987 M.D. degree, University of Lausanne 1989 Ph.D. degree, Karolinska Institute Board certifications 1994 Diplomate, American Board of Internal Medicine 1997 Diplomate, American Board of Medical Oncology Recertified through 2018 1999 Diplomate, American Board of Hematology Postdoctoral Research Training November 1989- Research fellow in the laboratory of Dr. Joseph Loscalzo, May 1992 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School January 1996- Research fellow in the laboratory of Dr. Joan Massagué, June 2000 Cell Biology Program, Howard Hughes Medical Institute and Sloan-Kettering Institute for Cancer Research Graduate Medical Training June 1992-June 1994 Internship and Residency in Medicine, The New York Hospital Cornell Medical Center July 1994-June 1997 Fellowship in Hematology/Oncology, Memorial Sloan-Kettering Cancer Center and the New York Hospital, Cornell University Medical College Clinical Appointments 1988-2000 Assistant in Medicine, Clinique Bon Port, Montreux, Switzerland 1993-2000 Assistant Physician I, The New York Hospital and the Memorial Sloan-Kettering Cancer Center-Cornell University Medical College 2001-2008 Attending Physician, Northwestern Memorial Hospital 2009- Attending Physician, UAB Hospitals Academic Appointments 1989-1992 Research Fellow in Medicine, Harvard Medical School 1992-2000 Clinical Associate in Medicine, Cornell University Medical College 2000-2005 Assistant Professor of Medicine Northwestern University Feinberg School of Medicine 2002-2008 Director, Cancer Genetics Program, Robert H. Lurie Comprehensive Cancer Center and Feinberg School of Medicine 2006-2008 Associate Professor of Medicine Northwestern University Feinberg School of Medicine 2006-2007 Co-Leader, Cancer Genes and Molecular Targeting Program, Robert H. Lurie Comprehensive Cancer Center 2008 Leader, Cancer Genes and Molecular Targeting Program, Robert H. Lurie Comprehensive Cancer Center 2008- Professor of Medicine with Tenure and Director, Division of Hematology/Oncology Division, The University of Alabama at Birmingham 2008-2009 Associate Director for Translational Research, The University of Alabama Comprehensive Cancer Center 2009-2011 Deputy Director, The University of Alabama Comprehensive Cancer Center 2008- Martha Ann and David L. May Endowed Chair in Cancer Research Editorial Positions 2003- Contributing Editor, The Journal of the American Medical Association (JAMA) 2004- Editor, The Journal of Experimental and Clinical Cancer Research Grant Review Panels 2010 Chair, Department of Defense Colorectal Cancer review panel 2010- Member, NCI Cancer Genetics (CG) Study section 2008- Member (adhoc), NCI Cancer Genetics (CG) Study section 2008- Member, AACR Colorectal Cancer Review Committee 2008 Member, Komen for the Cure Pathobiology-1 Review Panel 2007 Grant reviewer (adhoc), Instituto Toscano Tumori, Florence, Italy 2004- Member, Breast Cancer Center of Excellence and Era of Hope Scholar Award Review Panels, Department of Defense

Research/Clinical Interest Title Description Our laboratory focuses on three main projects: 1) The role of Transforming Growth Factor Beta (TGF-beta) in cancer development and progression, 2) The biological effects of amplitude-modulated electromagnetic fields, and 3) The role of variants of the adiponectin pathway in cancer development. 1) TGF-beta is one of the most potent inhibitor of normal cell growth and is also a potent modulator of the immune system. TGF-β signaling and growth-inhibition are mediated by the type I TGF-beta receptor (TGFBR1). We have previously identified a common mutant form of this gene, TGFBR1*6A, that is 9 base pairs shorter than TGFBR1. TGFBR1*6A is shorter than TGFBR1: it has a deletion of three GCG triplets coding for alanine within a nine alanine (9A) repeat of TGFBR1 exon 1 resulting in six alanines (6A) repeats. In normal epithelial cells TGFBR1*6A (*6A) mediates TGF-beta growth inhibitory signals less effectively than TGFBR1 (*9A). In cancer cells *6A is capable of switching TGF-beta growth inhibitory signals into growth stimulatory signals. This appears to be mediated by *6A signal sequence. Our laboratory has shown that *6A is somatically acquired in a large proportion of liver metastases from colon cancer. Epidemiological studies suggest that *6A is a candidate tumor susceptibility allele that is associated with an increased incidence of various types of cancer. Our discovery that decreased TGFBR1 signaling was associated with cancer risk led us to develop a novel mouse model of Tgfbr1 haploinsufficiency to test the hypothesis that constitutively decreased Tgfbr1 signaling enhances cancer risk. This mouse model led to the discovery that constitutively decreased TGFBR1 signaling is a potent modifier of colorectal cancer in mice and in humans. We are studying the molecular mechanisms underlying the biological effects of constitutively decreased TGFBR1 signaling. 2) We have previously shown that the intrabuccal administration of low and safe levels of electromagnetic fields, amplitude-modulated at a frequency of 42.7 Hz by means of a battery-powered portable device modifies the electroencephalographic activity of healthy subject, is associated with subjective and objective relaxation effects. We have also shown that sequential administration of four insomnia-specific frequencies, including 42.7 Hz, results in a significant decrease in sleep latency and a significant increase in total sleep time in patients suffering from chronic insomnia. This approach has been termed Low Energy Emission Therapy (LEET). Dosimetric studies have shown that the amount of electromagnetic fields delivered to the brain with this approach is 100 to 1000 times lower than the amount of electromagnetic fields delivered by handheld cellular phones and does not result in any heating effect within the brain. The U.S. FDA has determined that such a device is not a significant risk device. A long-term follow-up survey of 807 patients who have received this therapy revealed that the rate of adverse reactions were low and were not associated with increases in the incidence of malignancy or coronary heart disease. We hypothesized that the same approach may be used for the treatment of cancer. We have recently identified cancer-specific modulation frequencies, which have yielded therapeutic responses in patients with advanced cancer. We are studying the molecular mechanisms underlying the biological effects of cancer-specific amplitude-modulated electromagnetic fields. 3) Current epidemiologic evidence suggests an association between obesity, hyperinsulinemia and breast as well as colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. We have recently shown that common variants of the adiponectin and type I adiponectin receptor are associated with breast and colorectal cancer risk. We are currently studying the association of the adiponectin pathway with breast and colorectal cancer risk.

Selected Publications  Publication PUBMEDID Varga J, Pasche B. Transforming growth factor beta as a therapeutic target in systemic sclerosis. Nat Rev Rheumatol. 2009 Apr;5(4):200-6.   19337284  Zeng, Q., Phukan, S., Xu, Y., Sadim, M., Rosman, D., Pennison, M., Liao, J., Yang, G.-Y., Huang, C.-C., Valle, L., Di Cristofano, A., de la Chapelle, A., Pasche, B. Tgfbr1 haploinsufficiency is a potent modifier of colon cancer development Cancer Res 2009, 69:678-686   19147584  Varga, J., Pasche, B. Antitransforming growth factor-beta therapy in fibrosis: recent progress and implications for systemic sclerosis. Curr Opin Rheumatol 2008, 20(6):720-8   18946334  Kaklamani, V.G., Sadim, M., Koumantaki, Y., Kaklamanis, P., Pasche, B. Role of Polymorphisms in AdamantiadesBehçet's Disease Journal of Rheumatology 2008,35:2376-8   18925687  Kaklamani, V., Sadim, M., Do, A., Wisinski, K., Gulden, C., Offit, K., Baron, J., Ahsan, H., Mantzoros, C., Pasche, B. Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk Journal of the American Medical Association 2008, 300:1523-31 18827209   18827209  Kaklamani, V., Sadim, M., Hsi, A., Offit, K., Oddoux, C., Ostrer, H., Ahsan, H., Pasche, B., Mantzoros, C. Variants of the Adiponectin and Adiponectin 1 receptor genes and breast cancer risk Cancer Research 2008, 68:3178-3184   18451143  Bian, Y., Knobloch, T.J., Sadim, M., Kaklamani, V., Raji, A, Yang, G.-Y., Weghorst, C.M., Pasche, B. Somatic acquisition of TGFBR1*6A by epithelial and stromal cells during cancer development. Hum Mol Genetics 2007, 16: 3128-3135   17890272  Valle, L., Serena-Acedo, T., Liyanarachchi, S., Hampel, H., Comeras, I., Li, Z., Zeng, Q., Zhang, H.T., Pennison, M., Sadim, M., Pasche, B., Tanner, S., de la Chapelle, A. Germline allele-specific expression of TGFBR1 predisposes to colorectal cancer Science 2008, 321:1361-1365   1159397

Keywords TGF-beta cancer susceptibility treatment amplitude-modulated electromagnetic fields TGFBR1*6A

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